鎮痛剤の研究 (第3報)

鎮痛剤の連続投与に関する薬理学的研究

抄録

An appearance of tolerance and physical dependence was examined with 1, 4-bis-[(2-methoxy-4-propylphenoxy) acetyl] piperazine (AP-2) by analgesic administration to guinea pig and rat, comparing with that of morphine as a control. In the case when morphine was treated subcutaneously to guinea pig successively, it showed tolerance, however, AP-2 (200mg./kg.) did not display tolerance even when it was treated either peritoneally or per os consecutively (Figs. 3, 4).
A decrease of body weight, caused by physical dependence, was observed if the administration was discontinued or otherwise either levallorphan or AP-2 was administered instead of morphine, after the consecutive administration of morphine (100mg./kg.) to rat twice a day. However, no decrease of body weight was observed with the rat treated in advance by successive administration of AP-2 (200mg./kg.) twice a day, if the administration was discontinued or levallorphan was administered instead of AP-2.
To the tolerated guinea pig or rat with morphine, either suspension of water insoluble AP-2 or precipitated calcium carbonate was administered peritoneally, and a severe stretching symptom was displayed. It suggests that these tolerated animals with morphine were considered to be very sensitive to the stretcing reaction.